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Objective: to determine the diagnostic sensitivity and specificity of platelet indices [platelet count (PLT), mean platelet volume (MPV), MPV/PLT ratio] in sepsis. Study Design: Comparative cross-sectional study. Place and Duration of Study: Fauji Foundation Hospital, Rawalpindi Pakistan, from Jun to Dec 2019. Methodology: Adult patients (18-70 years old) with clinically diagnosed Sepsis (n=150) and their age-matched controls (n=150) were recruited. Platelet indices were measured, and blood culture samples were sent to the microbiology lab. Septic patients were compared to the control group. Receiver operating characteristic (ROC) curves were generated for diagnostic sensitivity and specificity of platelet indices. Results: Mean platelet volume and MPV/PLT ratios were significantly raised in sepsis, culture-positive sepsis and culture-negative sepsis compared to the control group. In ROC analysis, MPV had 67.3% sensitivity and 65% specificity, whereas the MPV/PLT ratio had 64.7 % sensitivity and 61% specificity to diagnose sepsis. Higher sensitivity (78%) and specificity (70%) were obtained in Culture positive cases for MPV as compared to sensitivity (64%) and specificity (59%) seen in Culture negative cases. MPV/PLT ratio showed the same sensitivity (64%) and specificity (61%) in both Culture positive and Culture negative cases. Conclusion: The study concludes that MPV and MPV/PLT ratios are significantly higher in sepsis, culture-positive sepsis and culture-negative sepsis than in the control. [ABSTRACT FROM AUTHOR]